Recent laboratory-based research integrating advances in ocular wavefront sensing and ophthalmic lens lathing has demonstrated that custom wavefront-guided soft contact lenses can be designed and manufactured for the highly aberrated eye. These lenses provide improved comfort, retinal image quality and visual performance over rigid lens corrections routinely prescribed for the highly aberrated eye. Unfortunately the processes required to provide such a lens to the patient are currently time consuming and too complex to be clinically viable or cost effective. To translate this laboratory work into clinical practice in a safe and efficient manner requires: 1) development of efficient methods to predictably control lens movement; 2) development of an efficient design process to intelligently implement individual optical corrections based on required lens movement and desired optical and visual performance levels; and 3) studies examining longitudinal efficacy and safety of these custom lenses. The specific aims of this 5 year grant are listed below and will directly address these issues in a sample population of highly aberrated eyes. The following hypotheses will be tested: 1. A multi-component stabilization technique comprised of corneal curve matching and traditional stabilization methods can be used to predictably and efficiently align the optical zone of a custom wavefront-guided soft contact lens to the optics of the highly aberrated eye. 2. A time and cost efficient, intelligent design process can be developed that quantitatively integrates measured lens movement, desired retinal image quality and desired visual performance into the design of a custom lens. 3. When worn in a daily wear manner, wavefront guided soft lens corrections provide a sustained improvement in optical quality, visual performance, comfort and wear time with a quantifiable increase in quality of life. The work proposed here is central to the mission of the NIH/NEI in that when successfully completed, it will translate laboratory research into clinical care that reduces visual impairment and improves the quality of life of individuals with highly aberrated eyes. PUBLIC HEALTH RELEVANCE: Custom wavefront guided soft contact lenses that compensate for both low order aberrations (sphere, cylinder) and high order aberrations (coma, trefoil, spherical aberration, etc) of the individual highly aberrated eye have been demonstrated on a small scale within multiple independent research laboratory settings. These early works show that custom soft contact lenses can be designed to meet or exceed the performance of current gold standard rigid forms of correction. However, these advances in soft lens technology come at the price of significant complexity in the design and manufacture process, making large-scale clinical deployment of custom contact lenses in their current form impossible. This raises the question: what obstacles must be overcome in order for custom wavefront guided soft contact lenses to attain clinical relevance? These obstacles can be summarized in three words: stabilization, optimization and demonstration. The specific aims in this grant will: 1) develop methods to allow for predictable stabilization of a custom soft contact lens on the eye; 2) examine methods that allow for the efficient and intelligent optimization of customized contact lens treatments that mitigate the effects of visually debilitating levels of optical aberration and 3) demonstration of the efficacy of custom soft contact lenses in a daily wear modality. Examination of these issues will result in the knowledge and tools necessary to capitalize on this promising new technology in the current clinical culture. It is hypothesized that successful completion of these aims will lead to methods allowing quantifiable improvements in optical performance, visual performance, comfort and quality of life for the individual that, due to disease, trauma or prior surgical intervention, suffers from highly aberrated optics of the eye. 1